A Study of the Efficacy and Safety of MK-0431D (a Fixed-dose Combination of Sitagliptin and Simvastatin) for the Treatment of Participants With Type 2 Diabetes Mellitus (T2DM) With Inadequate Glycemic Control on Metformin Monotherapy (MK-0431D-266)

Number of Participants Who Experienced at Least One Adverse Event (AE) [ Time Frame: Up to 16 weeks for non-serious AEs, up to 18 weeks for serious AEs ] [ Designated as safety issue: Yes ]

Excludes data after rescue therapy. Adverse event is defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the Sponsor's product, whether or not considered related to the use of the product.

Number of Participants Who Discontinued Study Drug Due to an Adverse Event [ Time Frame: Up to 16 weeks ] [ Designated as safety issue: Yes ]

Excludes data after rescue therapy. Adverse event is defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the Sponsor's product, whether or not considered related to the use of the product.

A Study of the Efficacy and Safety of MK-0431D (a Fixed-dose Combination of Sitagliptin and Simvastatin) for the Treatment of Participants With Type 2 Diabetes Mellitus (T2DM) With Inadequate Glycemic Control on Metformin Monotherapy (MK-0431D-266)

Official Title ICMJE

A Phase III, Randomized, Double-blind, Clinical Trial to Study the Efficacy and Safety of MK-0431D (a Fixed-dose Combination [FDC] of Sitagliptin and Simvastatin) for the Treatment of Patients With Type 2 Diabetes Mellitus (T2DM) With Inadequate Glycemic Control on Metformin Monotherapy

Brief Summary

The purpose of this study is to assess the efficacy and safety of sitagliptin/simvastatin fixed-dose combination (FDC) in participants with T2DM who have inadequate glycemic control while on metformin monotherapy. The primary hypothesis of this study is that after 16 weeks of therapy, the mean change from baseline in hemoglobin A1C (A1C) in participants treated with sitagliptin/simvastatin FDC is non-inferior compared to sitagliptin alone.

Participants will continue on their stable, pre-screening metformin daily dose of >= 1500 mg for at least 12 weeks prior to randomization and during the study

Other Names:

Fortamet®

Glucophage®

Glucophage® XR

Glumetza®

Riomet®

Metgluco®

Glycoran®

Drug: Glimepiride

Following randomization, participants requiring glycemic rescue may receive open-label glimepiride initiated at a dose of 1 mg/day or 2 mg/day which may be up-titrated to 6 mg/day taken once daily with breakfast or the first main meal of the day.

Other Names:

Amaryl®

Glimy

Study Arm (s)

Experimental: Sitagliptin/Simvastatin FDC

Sitagliptin 100 mg/simvastatin 40 mg FDC plus placebo to sitagliptin plus placebo to simvastatin administered orally once daily in the evening for 16 weeks. Participants will continue on their stable pre-screening metformin dose and dosing regimen of >=1500 mg daily for the duration of the study. Participants may receive glimepiride 1 mg once daily or 2 mg once daily (may be up-titrated to 6 mg once daily) as rescue therapy.

Interventions:

Drug: Sitagliptin/Simvastatin FDC

Drug: Placebo to sitagliptin

Drug: Placebo to simvastatin

Drug: Metformin

Drug: Glimepiride

Active Comparator: Sitagliptin

Sitagliptin 100 mg plus placebo to simvastatin plus placebo to sitagliptin/simvastatin FDC administered orally once daily in the evening for 16 weeks. Participants will continue on their stable pre-screening metformin dose and dosing regimen of >=1500 mg daily for the duration of the study. Participants may receive glimepiride 1 mg once daily or 2 mg once daily (may be up-titrated to 6 mg once daily) as rescue therapy.

Interventions:

Drug: Sitagliptin

Drug: Placebo to simvastatin

Drug: Placebo to Sitagliptin/Simvastatin FDC

Drug: Metformin

Drug: Glimepiride

Active Comparator: Simvastatin

Simvastatin 40 mg plus placebo to sitagliptin plus placebo to sitagliptin/simvastatin FDC administered orally once daily in the evening for 16 weeks. Participants will continue on their stable pre-screening metformin dose and dosing regimen of >=1500 mg daily for the duration of the study. Participants may receive glimepiride 1 mg once daily or 2 mg once daily (may be up-titrated to 6 mg once daily) as rescue therapy.

Interventions:

Drug: Simvastatin

Drug: Placebo to sitagliptin

Drug: Placebo to Sitagliptin/Simvastatin FDC

Drug: Metformin

Drug: Glimepiride

Publications *

Not Provided

* Includes publications given by the data provider as well as publications
identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.

(1) Male; (2) female not of reproductive potential; or (3) female of reproductive potential who agrees to remain abstinent or use alone or in conjunction with their partner 2 methods of contraception to prevent pregnancy during the study and for 14 days after the last dose of study drug

is currently on metformin monotherapy at a daily dose of at least 1500 mg for at least 10 weeks

is not on a lipid-lowering agent for at least 6 weeks prior to entering the study

Exclusion Criteria:

has history of type 1 diabetes mellitus (T1DM), or a history of ketoacidosis or possibly has T1DM

has been on a thiazolidinedione (TZD) within the previous 16 weeks

has been treated with a statin or other lipid-lowering agent (including over-the-counter [OTC] supplements) within the previous 6 weeks

currently participating in or has participated in another clinical study within the past 12 weeks

intends to consume >1.2 liters of grapefruit juice daily during the study

is on or likely to require treatment for at least 2 consecutive weeks or repeated courses of corticosteroids (inhaled, nasal and topical corticosteroids are permitted)

intolerance or hypersensitivity to sitagliptin, simvastatin, metformin or glimepiride

is on a weight loss program and not in the maintenance phase or has started a weight loss medication or has undergone bariatric surgery in the previous 12 months

has undergone a surgical procedure in the past 4 weeks or planned major surgery during the study

has symptomatic hyperglycemia that requires immediate initiation, adjustment, or addition of antihyperglycemic therapy

has a history of myopathy or rhabdomyolysis with any statin

has cardiovascular disease, a diagnosis of congestive heart failure, or uncontrolled high blood pressure